Calabrese E J, Baldwin L A
Department of Environmental Health Sciences, School of Public Health, University of Massachusetts, Amherst, Massachusetts, 01003, USA.
Regul Toxicol Pharmacol. 1998 Dec;28(3):230-41. doi: 10.1006/rtph.1998.1267.
The concept of hormesis (i.e., low-dose stimulation/high-dose inhibition) has been shown to be widely generalizable with respect to chemical class, animal model, gender, and biological end point. The public health implication of this lack of linearity in the low-dose area of the dose-response curve raises the question of whether low doses of carcinogens will reduce cancer risk. Articles relating to the process of carcinogenesis (i.e., initiation, promotion, tumor development, and progression) were obtained from a recently developed chemical hormesis database and evaluated for their evidence of hormesis. Numerous examples in well-designed studies indicate that U- or J-shaped dose-response relationships exist with respect to various biomarkers of carcinogenesis in different animal models of both sexes. Examples of such J-shaped dose-response relationships in each stage of the process of carcinogenesis were selected for detailed toxicological examination. These results have important implications for both the hazard assessment of carcinogens and cancer risk assessment procedures.
毒物兴奋效应的概念(即低剂量刺激/高剂量抑制)已被证明在化学类别、动物模型、性别和生物学终点方面具有广泛的通用性。剂量反应曲线低剂量区域缺乏线性关系对公共卫生的影响引发了一个问题,即低剂量致癌物是否会降低癌症风险。从最近开发的化学毒物兴奋效应数据库中获取了与致癌过程(即启动、促进、肿瘤发展和进展)相关的文章,并对其毒物兴奋效应的证据进行了评估。精心设计的研究中的大量例子表明,在不同性别的不同动物模型中,各种致癌生物标志物存在U形或J形剂量反应关系。选择致癌过程各阶段中此类J形剂量反应关系的例子进行详细的毒理学检查。这些结果对致癌物的危害评估和癌症风险评估程序都具有重要意义。